首页> 外文期刊>Diabetes >MicroRNAs miR-23a-3p, miR-23b-3p, and miR-149-5p Regulate the Expression of Proapoptotic BH3-Only Proteins DP5 and PUMA in Human Pancreatic β-Cells
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MicroRNAs miR-23a-3p, miR-23b-3p, and miR-149-5p Regulate the Expression of Proapoptotic BH3-Only Proteins DP5 and PUMA in Human Pancreatic β-Cells

机译:MicroRNA miR-23a-3p,miR-23b-3p和miR-149-5p调节人胰腺β细胞中仅凋亡的BH3蛋白DP5和PUMA的表达

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摘要

Type 1 diabetes (T1D) is an autoimmune disease leading to β-cell destruction. MicroRNAs (miRNAs) are small non-coding RNAs that control gene expression and organ formation. They participate in the pathogenesis of several autoimmune diseases, but the nature of miRNAs contributing to β-cell death in T1D and their target genes remain to be clarified. We performed an miRNA expression profile on human islet preparations exposed to the cytokines IL-1β plus IFN-γ. Confirmation of miRNA and target gene modification in human β-cells was performed by real-time quantitative PCR. Single-stranded miRNAs inhibitors were used to block selected endogenous miRNAs. Cell death was measured by Hoechst/propidium iodide staining and activation of caspase-3. Fifty-seven miRNAs were detected as modulated by cytokines. Three of them, namely miR-23a-3p, miR-23b-3p, and miR-149-5p, were downreg-ulated by cytokines and selected for further studies. These miRNAs were found to regulate the expression of the proapoptotic Bcl-2 proteins DP5 and PUMA and consequent human p-cell apoptosis. These results identify a novel cross talk between a key family of miRNAs and proapoptotic Bcl-2 proteins in human pancreatic β-cells, broadening our understanding of cytokine-induced β-cell apoptosis in early T1D.
机译:1型糖尿病(T1D)是导致β细胞破坏的自身免疫性疾病。 MicroRNA(miRNA)是控制基因表达和器官形成的小型非编码RNA。它们参与了几种自身免疫性疾病的发病机制,但是导致T1D中β细胞死亡的miRNA及其靶基因的性质仍有待阐明。我们对暴露于细胞因子IL-1β加IFN-γ的人胰岛制剂进行了miRNA表达谱分析。通过实时定量PCR对人β细胞中的miRNA和靶基因修饰进行确认。使用单链miRNA抑制剂来封闭选定的内源性miRNA。细胞死亡通过Hoechst /碘化丙啶染色和caspase-3活化来测量。检测到57种miRNA受细胞因子调节。它们中的三个,即miR-23a-3p,miR-23b-3p和miR-149-5p,已被细胞因子下调,并选择用于进一步研究。发现这些miRNA调节促凋亡的Bcl-2蛋白DP5和PUMA的表达以及随之而来的人类p细胞凋亡。这些结果确定了人类胰腺β细胞中miRNA的关键家族与促凋亡Bcl-2蛋白之间的新型相互作用,从而拓宽了我们对T1D早期细胞因子诱导的β细胞凋亡的理解。

著录项

  • 来源
    《Diabetes》 |2017年第1期|100-112|共13页
  • 作者单位

    ULB Center for Diabetes Research, Medical Faculty, Universite Libre de Bruxelles, Brussels, Belgium;

    Diabetes Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy,Umberto Di Mario ONLUS Foundation-Toscana Life Sciences Foundation, Siena, Italy;

    ULB Center for Diabetes Research, Medical Faculty, Universite Libre de Bruxelles, Brussels, Belgium;

    ULB Center for Diabetes Research, Medical Faculty, Universite Libre de Bruxelles, Brussels, Belgium;

    ULB Center for Diabetes Research, Medical Faculty, Universite Libre de Bruxelles, Brussels, Belgium;

    ULB Center for Diabetes Research, Medical Faculty, Universite Libre de Bruxelles, Brussels, Belgium;

    Department of Fundamental Neurosciences, University of Lausanne, Lausanne, Switzerland;

    Department of Fundamental Neurosciences, University of Lausanne, Lausanne, Switzerland;

    Islet Cell Laboratory, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy;

    Islet Cell Laboratory, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy;

    Diabetes Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy,Umberto Di Mario ONLUS Foundation-Toscana Life Sciences Foundation, Siena, Italy;

    ULB Center for Diabetes Research, Medical Faculty, Universite Libre de Bruxelles, Brussels, Belgium;

  • 收录信息 美国《科学引文索引》(SCI);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
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  • 入库时间 2022-08-18 03:46:06

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